The aim of this project is to improve the treatment of small cell carcinoma (SCC) of the lung by learning more about the pathobiology of this tumor. This is being approached by measuring tumor production of neurohypophysial principles (vasopressin (VP), oxytocin (OT), vasotocin (VT) and their associated neurophysins (HNPs)); and additionally of corticotrophin-like intermediate lobe peptide (CLIP) using specific radioimmunoassays (RIAs). Other methods will include pulse-labelling, polyacrylamide electrophoresis and isofocusing, high-pressure liquid chromatography, affinity chromatography, cell culture, amino acid analysis and protein sequencing. There is every reason to believe, on the basis of our initial studies on plasma from patients, that RIAs for HNPs, and possibly also for VP, OT, and VT, can be used effectively in the treatment of over 60% of patients with SCC of the lung. By developing an RIA to CLIP we feel that we can extend our evaluations to include all, or almost all, patients with SCC. We will use our specific antibodies to develop rapid immunoassays for possible use as even more effective tools to monitor treatment and as potential screening procedures for SCC. The rate and mode of production/release of HNPs and VP, OT and VT will be determined in cultures of SCC, and at least one such culture which produces vasopressin-associated neurophysin and VP has already been developed at Dartmouth. Knowledge of the rates of production/release of VP, OT, VT and HNPs by tumor cells in vitro might allow the amount of residual tumor to be determined in patients during treatment, while information concerning the biosynthesis, storage and release of these substances by tumor cells could lead to a better understanding of the pathobiology of SCC and to a more rational therapy. Our calculations suggest that we can probably monitor residual tumor that is about 100-fold smaller than that which can be observed by other diagnostic means, and this is supported by studies conducted thus far using RIAs to HNPs. Use of our RIAs may allow therapy to be pushed to the point where no more tumor remains; and moreover, should allow us to forecast tumor growth following remission. Data will be evaluated through NIH Coop. Study, Acute Leukemia, Group B. Nos.7781 and 7782, of which Dr. H. L. Maurer is a Co-Chairman.